The overall objectives of this project are: 1) to determine the factors regulating the levels and composition of the plasma lipoproteins, 2) to study the struture of the lipoproteins and determine how this structure affects the biological function of the lipoproteins, and 3) to isolate the various apolipoproteins of the rat lipoproteins and to characterize them by chemical and physical methods in order to relate physiologic studies in the rat model to studies in other species, especially man. To achieve these ends we shall continue studies of measures which alter the levels of lipoproteins and alter their apolipoprotein composition. These measures include dietary perturbation of pathophysiologic perturbations such as the induction of diabetes mellitus. We propose to study the mechanism of the production of hyperlipidemia by these various measures, attempting to detemine whether the increased levels of certain of the lipoprotein fractions are due to increased formation of lipoproteins or decreased removal of lipoproteins from the circulation. In the course of these studies we shall pay special attention to the role of the various apolipoproteins in the metabolism of lipoproteins to determine whether alterations in the apolipoprotein composition affect the metabolism of a given lipoprotein class or family. We propose to study the role of specific apolipoproteins in the binding of lipoproteins to cells in tissue culture. In doing this we shall take advantage of the fact that the various dietary and metabolic changes that we have induced in rats have produced lipoproteins of altered apolipoprotein composition. Finally, we shall continue our studies of the free apolipoproteins in plasma attempting to determine whether they are native or artifactual. We shall characterize these free apolipoproteins and determine their possible physiologic significance.